Everolimus in Treating Women With Breast Cancer That Can Be Removed by Surgery

This study has been withdrawn prior to enrollment.
(Withdrawn due to no accrual)
Sponsor:
Information provided by:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00855114
First received: March 3, 2009
Last updated: August 11, 2011
Last verified: August 2011
  Purpose

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well everolimus works in treating women with breast cancer that can be removed by surgery.


Condition Intervention Phase
Breast Cancer
Drug: everolimus
Procedure: therapeutic conventional surgery
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Short-Term Everolimus (RAD001) to Predict Response in Women With Operable Breast Cancer

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Decrease of total choline in at least 30% of patients [ Time Frame: Pre-Treatment Compared to Post-Treatment (Day 7) ] [ Designated as safety issue: No ]
    Choline is measured by magnetic resonance imaging (MRI/MRS) scan.


Secondary Outcome Measures:
  • Identification of response to everolimus by activated mTOR signaling [ Time Frame: Pre-Treatment Compared to Post-Surgery (Day 7) ] [ Designated as safety issue: No ]
    Two core biopsies will be obtained at the time of diagnostic biopsy. Waste tumor tissue obtained during surgery will be collected at the time of surgery. It will be stored under liquid nitrogen until they can be examined for activation of mTOR targets, specifically, 4E-BP1, p70S6 kinase phosphorylation, and activity of cap dependent translational complex.


Enrollment: 0
Study Start Date: July 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients Treated with Everolimus
Breast cancer patients treated with Everolimus by mouth, 5 mgs/day x 7 days, followed by surgery.
Drug: everolimus
5 mg/day x 7 days by mouth
Other Names:
  • RAD001
  • Afinitor(R)
Procedure: therapeutic conventional surgery
Definitive excision of breast cancer tissue
Other Name: surgery

Detailed Description:

OBJECTIVES:

Primary

  • Determine whether the administration of everolimus results in a decrease of total choline, a surrogate marker of response, in at least 30% of women with resectable breast cancer.

Secondary

  • Determine whether tumors with activated mTOR signaling, as measured by phosphorylation of 4E-BP1 and activity of cap dependent translational complex, will identify those women responsive to everolimus.

OUTLINE: Patients receive oral everolimus once daily on days 1-7 in the absence of disease progression or unacceptable toxicity. Within 24 hours after completing everolimus, patients undergo surgery.

Tumor tissue samples are collected at baseline and during surgery for the analysis of mTOR targets (i.e., 4E-BP1, p70S6 kinase phosphorylation), Ki67, cleaved caspase 3, and activity of cap dependent translational complex by immunohistochemical assays. Patients also undergo MRI/MRS before and after everolimus therapy for total choline and glucose levels measurement.

After completion of study therapy, patients are followed for 30 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of invasive breast cancer

    • Resectable disease
  • Measurable disease, defined as a primary breast mass > 2.0 cm by breast imaging or clinical exam
  • Planning to undergo surgical resection after neoadjuvant therapy
  • Menopausal status not specified
  • Eastern Clinical Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin > 9.0 g/dL
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • Total bilirubin ≤ 1.5 times ULN
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion Criteria:

  • Intracranial disease
  • Hormone receptor status not specified
  • Obese (> 250 pounds)
  • Immunosuppression from any cause (e.g., known HIV infection)
  • History of severe asthma and/or allergies
  • History of severe claustrophobia
  • Ferromagnetic implants, history of shotgun wound and/or shrapnel, cardiac pacemakers, or other similar situations that would be contrary to strong magnetic force
  • Bleeding diathesis
  • Unstable systemic disease, including but not limited to, any of the following:

    • Uncontrolled diabetes
    • Severe infection
    • Severe malnutrition
    • Uncontrolled hypertension
    • Unstable angina
    • Ventricular arrhythmias
    • Active ischemic heart disease
    • Congestive heart failure
    • Myocardial infarction within the past 6 months
    • Chronic liver disease
    • Renal disease
    • Active upper gastrointestinal tract ulceration
  • Less than 4 weeks since prior investigational drug
  • Prior therapy with sirolimus or its analogues
  • Concurrent immunosuppressive therapy (e.g., steroids, cytotoxic agents, or concurrent radiotherapy)
  • Concurrent anticoagulation (i.e., coumadin)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00855114

Locations
United States, Minnesota
University of Minnesota Children's Hospital - Fairview
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Douglas Yee, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Douglas Yee, Masonic Cancer Center at University of Minnesota
ClinicalTrials.gov Identifier: NCT00855114     History of Changes
Other Study ID Numbers: 2005LS029, 0505M70026
Study First Received: March 3, 2009
Last Updated: August 11, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
stage II breast cancer
stage III breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 18, 2014